Trends in Endocrinology & Metabolism
ReviewGlucagon-like Peptide 2
Section snippets
GLP-2 Synthesis, Secretion and Physiology
GLP-2, a 33 amino acid (aa) peptide, is highly conserved across different mammalian species. Like GLP-1, GLP-2 is secreted from enteroendocrine cells in a nutrient-dependent manner in both rodents and humans10, 11. Both GLP-1 and GLP-2 contain an alanine residue at position 2, rendering them ideal substrates for cleavage and inactivation by the enzyme dipeptidyl peptidase 4 (DPP-IV). Indeed, both GLP-2 (aa 1–33) and GLP-2 (aa 3–33) are detected in plasma from fasting rats and humans, and the
GLP-2 Action in Experimental Models of Intestinal Atrophy and Injury
A combination of biliary secretions, nutrients and growth factors is known to be important for maintenance and growth of the intestinal mucosal epithelium22. After fasting or parenteral feeding, intestinal weight drops rapidly in both the small and large bowel, primarily as a result of mucosal atrophy. Remarkably, co-infusion of GLP-2 and total parenteral nutrition (TPN) in fasted rats prevented mucosal atrophy and restored intestinal weight in the small, but not the large bowel23. These
Mechanism of GLP-2 Action
Most data on GLP-2 action derive from studies administering pharmacological amounts of GLP-2 or GLP-2 analogs to rodents. Although in- creased endogenous GLP-2 is associated with intestinal mucosal hyperplasia, GLP-2 antagonists are not yet widely available, and studies reporting immunoneutralization of GLP-2 action have not been reported. Furthermore, no animal models or human reports of GLP-2 deficiency have been reported, hence the central physiological significance of GLP-2 action for
GLP-2: Unanswered Questions
Although our understanding of GLP-2 action has advanced rapidly over the past several years, many important physiological questions remain unanswered. The relative physiological importance of GLP-2 for intestinal growth, adaptation to intestinal injury and maintenance of intestinal barrier function await studies using GLP-2 antagonists, immunoneutralizing GLP-2 antisera or GLP-2R knockout mice. Whether GLP-2 has an important role in the stomach or esophagus awaits further study. The precise
Acknowledgements
Work from the Drucker laboratory was supported by grants from the Medical Research Council of Canada and Allelix Biopharmaceuticals Inc. DJD is a Scientist of the Medical Research Council of Canada and a consultant to Allelix Biopharmaceuticals Inc.
References (25)
- et al.
Oxyntomodulin and its C-terminal octapeptide inhibit liquid meal-stimulated acid secretion
Peptides
(1986) - et al.
Preproglucagon gene expression in pancreas and intestine diversifies at the level of post-translational processing
J. Biol. Chem.
(1986) - et al.
Human glucagon-like peptides 1 and 2 activate rat brain adenylate cyclase
FEBS Lett.
(1984) - et al.
The primary structure of porcine glicentin (proglucagon)
Regul. Pept.
(1982) - et al.
Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not pancreas
Endocrinology
(1986) The glucagon-like peptides
Diabetes
(1998)- et al.
Endocrine tumour in kidney affecting small bowel structure, motility, and absorptive function
Gut
(1971) - et al.
Glucagonoma syndrome demonstrating giant duodenal villi
Gut
(1984) - et al.
Induction of intestinal epithelial proliferation by glucagon-like peptide 2
Proc. Natl. Acad. Sci. U. S. A.
(1996) - et al.
Radio-immunoassays for glucagon-like peptides 1 and 2 (GLP-1 and GLP-2)
Scand. J. Clin. Lab. Invest.
(1987)
Circulating and tissue forms of the intestinal growth factor, glucagon-like peptide 2
Endocrinology
Regulation of the biological activity of glucagon-like peptide 2 by dipeptidyl peptidase IV
Nat. Biotechnol.
Cited by (50)
Effects of centrally injected glucagon-like peptide-2 on gastric mucosal blood flow in rats: Possible mechanisms
2015, PeptidesCitation Excerpt :GLP-1 is a glucose-dependent insulinotropic hormone and it also regulates various gastric and cardiovascular functions [4–7]. On the other hand, the physiological role of GLP-2 has not been discovered until 1996, when it has been shown to stimulate the mucosal epithelial proliferation in the rat small intestine [8,9]. Due to its intestinotrophic effects, GLP-2 has been suggested to have a potential therapeutic role in “the short bowel syndrome” [8,10,11].
Central GLP-1 Actions on Energy Metabolism
2010, Vitamins and HormonesCitation Excerpt :Another product generated by the posttranslational processing of proglucagon is GLP-2, which is also secreted from the intestinal L cells mainly located in the ileum and the colon. GLP-2 has beneficial effects on intestinal growth (Drucker, 1999; Jeppesen, 2003), and its actions are mediated by a specific GLP-2R (Munroe et al., 1999). In addition to mediating increased small bowel absorption through induction of epithelial proliferation, GLP-2 has been described to decrease gastric emptying (Wojdemann et al., 1998), increase intestinal transit time (Wojdemann et al., 1999), and inhibit sham feeding-induced gastric acid secretion (Wojdemann et al., 1999).
Gastrointestinal hormones and food intake
2005, GastroenterologyThe combination of metformin and a dipeptidyl peptidase IV inhibitor prevents 5-fluorouracil-induced reduction of small intestine weight
2004, European Journal of PharmacologyCentral control of body weight and appetite
2008, Journal of Clinical Endocrinology and MetabolismGlucose transporters in the small intestine in health and disease
2020, Pflugers Archiv European Journal of Physiology